P-Quinol acetates

Hydroxylation at C-5 or C-l3 has also been successfully achieved by lead tetraacetate oxidation, which was extensively studied in connection with isoquinoline alkaloids by Umezawa s group. (+)-Govanine (96) and (+)-discretine (97) were oxidized with lead tetraacetate in acetic acid to afford 5-acetoxy products 100,101, and 102 via p-quinol acetates (e.g., 99) (Scheme 23)... 

Hydroxyprotoberberine 59a and ( )-corytencine (98) led to 13-acetoxy compounds 104,105, and 107 moreover, the 2,3,9,10,12-pentaoxy-genated protoberberine 108 was also obtained from 98 via the p-quinol acetate 106 through a retro-Mannich reaction followed by recyclization (74,75). Oxidation in dichloromethane instead of acetic acid proceeded differently, namely, 97 and 98 led to pentaoxygenated protoberberines 103 and 109 by introduction of an acetoxyl group at C-4 and C-12, respectively, via o-quinol acetates (76). 

Lead tetraacetate oxidation was applied to construct a benzo[c]-phenanthridine skeleton. The Hofmann degradation product 224 derived from the phenolic protoberberine 59a was oxidized with lead tetraacetate to afford the p-quinol acetate 225, which was cyclized to the benzo[c]-... 

Lead tetraacetate in acetic acid oxidizes phenolic 1-benzylisoquinolines to p-quinol acetates which usually rearrange to aporphines in trifluoroacetic acid (25). However, Blasko et al. (24) recently reported that lead tetraacetate oxidized ( )-A -norlaudanosine (34) to dibenzopyrrocoline 35 in 16% yield. 

A full paper has appeared describing the synthesis of the aporphines (34) and (35) through treatment of the p-quinol acetate (33) with trifluoroacetic acid.46 The non-identity of (35) with natural lirinine confirmed structure (36) for lirinine. 

The migration of oxygen from a quaternary center in a cyclohexadienone may be preferred to a carbon shift, when present as an ether or ester function rather than free hydroxy. Thus the p-quinol acetate (117) yields the orcinol monoacetate (118 79%) on treatment at room temperature with trifluoroacetic anhydride, and the p-quinol ether (119) forms the resorcinol diethyl ether (120 71%) in ethanolic sulfuric acid. In the second case, hemiketalization must intervene also some methyl shift (12%) is observed. With the quinol (121), treatment with acetic anhydride-sulfuric acid leads to the lactone (122) acetylation or lactonization probably precedes oxygen shift. A number of related examples can be found in the steroid area. - Thermal 1,3-shifts of p-quinol acetates can also be induced acetate (117) yields catechol acetate (123 50-60%, 45 °C) by way of isomerization of the first-formed acetate (124). In the o-quinol acetate series, 1,2-acetoxy shift is seen in (125) (126 92%) and in (127) (128 90%), both in... 

Dimethylphenol (206) was treated with NaBiOs in benzene to afford polyphenylene oxide (659) and 3,3, 5,5 -tetramethyldiphenoquinone (207) in 74 and 12% yields, respectively . This result is similar to that of Mn02 oxidation (see Scheme 126). In contrast, the use of AcOH instead of benzene as a solvent provided the corresponding quinol acetate 864 and 207 in 38 and 15% yields, respectively (Scheme 174) °. Oxidation of 2,4,6-tri(tert-butyl)phenol (73) with NaBiOs in AcOH afforded the p-quinol acetate (865) as a major product (62%) and the o-quinol acetate (866) as a minor product (22%). In contrast, Pb(OAc)4 oxidation of 73 in AcOH provided 866 as a main product (60%) (see Scheme 170). Oxidation of alkoxyphenols and other phenols has also been studied . ... 

In the early 1970s, our attention was directed to the Wessely acetoxy-lation (13). LTA oxidation of phenolic tetrahydroisoquinolines was exploited in our laboratory to give the corresponding p-quinol acetates, which were proved to be the reactive intermediates for the aporphine synthesis (14-15)-, that is, when an electron-rich benzene ring was present in a given p-quinol acetate, C-C bond formation occurred intramolecu-larly on its acid treatment. 

Since many isoquinoline alkaloids incorporate a guiacol moiety, we first tried to oxidize the most accessible 6-methoxy- and 7-methoxy-l,2,3,4-tetrahydroisoquinolinols (types A and B) with LTA. Later, tetrahydro-isoquinolinols of type C were also used. In spite of Wessely s statement (16) that LTA oxidation of both vanillin and isovanillin affords the corresponding o-quinol acetates, for a while we were able to obtain not the o-quinol acetate 2 from corypalline (1) but the p-quinol acetate 3 (17). At the outset of our study (IS), LTA oxidation of isocorypalline (4) gave no isolable o-quinol acetate 5, 4-acetoxyisocorypalline (6) being isolated instead. 

Aporphine synthesis via a p-quinol acetate was first achieved in our laboratory (14,15). LTA oxidation in AcOH of ( )-codamine (11) gave a p-quinol acetate (12) (Scheme 2), the structure of which was characterized by spectroscopic means. Treatment of acetate 12 with acetic anhydride in the presence of concentrated sulfuric acid gave ( )-( -acetylthaliporphine... 

Surprisingly, TFA treatment in CH2CI2 of the p-quinol acetate derived from ( )-l-benzyl-8-chloro-l, 2,3,4-tetrahydroisoquinolin-7-ols gave three products (37,38), in spite of the expectation that the reaction might afford... 

Coutts cZ al. (41) reported that LTA oxidation in AcOH of ( )-2-tri-fluoroacetyl - ], 2,3,4 - tetrahydro - 6- methoxy -1 - (3,4,5 - trimethoxybenzyl) iso-quinolin-7-ol (60) gives p-quinol acetate 61, TFA treatment in CHiCL of which affords in 35% yield ( )-6-trifluoroacetyl-l-hydroxy-2,9,10,11-tetramethoxynoraporphine (62). Further methylation of 62 with methyl iodide and sodium hydride gave ( )-6-trifluoroacetyI-l, 2,9,10,11-pentamethoxynoraporphine (63) (Scheme 8). 

A modification of the above procedure gave three types of products, C-homoaporphines 129-131, homoproaporphines 132 and 133 (see Section IV), and homomorphinandienones 134 and 135 (except for 118 see Section V) (57). LTA oxidation in AcOH of ( )-l-phenethyltetrahydro-isoquinolin-7-ol 117 gave a p-quinol acetate l20, TFA treatment of which in CH2CI2 produced the ( )-C-homoaporphine 129 in 44.2% yield. Similarly, the ( )-C-homoaporphines 130 and 131 were prepared in 55 and 35.2% yield, respectively, from the ( )-l-phenethyltetrahydro-isoquinolin-7-ols 118 and 119 (Scheme 15). 

In contrast to the above results, TFA treatment of p-quinol acetate 200 of ( )-I-(4-methoxyphenethyl)-tetrahydroisoquinolin-7-ol 199 proceeded smoothly to give ( )-l-hydroxy-2-methoxyhomoproaporphine (201) in 98% yield (64). Alternatively, treatment of 200 with acetic anhydride containing concentrated sulfuric acid produced ( )-l-acetoxy-2-methoxyhomoproaporphine (202) and the ( )-4j8-acetoxylated homo-proaporphine 203 (see Section XII,B) in 53 and 5% yield, respectively (Scheme 21). 

As mentioned above (see Section ILA), a diastereomeric mixture of ( )-4)3- and ( )-4a-acetoxy-O-acetylthaliporphines (18 and 19) was formed as a by-product on acid treatment of the p-quinol acetate derived... 

LTA oxidation of four tetrahydroprotoberberines has been investigated (110,111). Namely, LTA oxidation in AcOH of ( )-govanine (366) and ( )-10-hydroxy-2,3,l 1-trimethoxytetrahydroprotoberberine (369) afforded the corresponding p-quinol acetates 367 and 370 quantitatively. Treatment of acetate 367 with acetic anhydride including concentrated sulfuric acid gave only ( )-2,5 -diacetoxy-3,10,11-trimethoxy tetrahydroprotoberberine (368) in 90.9% yield, whereas that of acetate 370 resulted in acetoxylation at C-13 to lead to ( )-10,13q - and ( )-10,13 /3-diacetoxy-... 

As mentioned in Section VI, acid treatment of the p-quinol acetates of... 

A synthesis of bistetrahydroisoquinolines using p-quinol acetate 3 and 8,8a-epoxy p-quinol 495 was performed (130-132). Reaction of 3 cory-palline (1) (130), isocorypalline (4), and 6- and 7-tetrahydroisoquinolinols (131) and subsequent acetylation gave substituted bistetrahydroisoquinolines 487-492 (Scheme 64). Interestingly, similar treatment of 3 with... 

Oxidation of phenols. Phenols are oxidized by lead tetracetate to o- and p-quinol acetates or biphenyls depending on reaction conditions. For example,... 

The total syntheses of the less common alkaloids cassamedine (35f) (427) and N-methylovigerine (25n) (458), and of some nornucipherine derivatives were also achieved (459). Thaliporphine (24g), domesticine (241), and glaucine (24h), can be synthesized via the p-quinol acetate route (415, 460, 461) (Scheme 11). 

Scheme 11. Synthesis of the aporphine alkaloids (24) via the p-quinol acetate route (413).

A new route to aporphines involves treatment of codamine (81) with lead tetra-acetate to yield the p-quinol acetate (82). Further treatment with acetic anhydride and sulphuric acid generates 0-acetylthaliporphine (83) (14%) and 4-acetoxy-O-acetylthaliporphine (84) (6%). ... 

The synthetic method using p-quinol acetates to prepare aporphines has been extended to the synthesis of ( )-kreysigine (220). Treatment with acid of the p-quinol acetate (225a) derived from ( + )-(225) gave ( )-0-acetylkreysigine in 18%yield.2 5... 

A soln. of tetralin-p-quinol acetate in glacial acetic acid treated with a satd. soln. of 2,4-dinitrophenylhydrazine in glycol monomethyl ether, and allowed to stand 24 hrs. at room temp. 2,4-dinitrobenzeneazo-6-tetralin. Y 96%. E. Hecker, B. 92, 1386 (1959) also with p-toluenesulfonic acid as catalyst s. B. 92, 3198. 

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